Description: Homo sapiens KRIT1, ankyrin repeat containing (KRIT1), transcript variant 1, mRNA. RefSeq Summary (NM_194456): This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]. Transcript (Including UTRs) Position: hg19 chr7:91,828,283-91,875,414 Size: 47,132 Total Exon Count: 20 Strand: - Coding Region Position: hg19 chr7:91,830,050-91,871,449 Size: 41,400 Coding Exon Count: 16
ID:KRIT1_HUMAN DESCRIPTION: RecName: Full=Krev interaction trapped protein 1; Short=Krev interaction trapped 1; AltName: Full=Cerebral cavernous malformations 1 protein; FUNCTION: Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits EKR1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. SUBUNIT: Interacts with RAP1A. Interacts with CDH5. Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1 (By similarity). Interacts (via FERM domain) with RAP1B. INTERACTION: Q9BSQ5:CCM2; NbExp=3; IntAct=EBI-1573121, EBI-1573056; SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. Cell junction. Note=KRIT1 and CDH5 reciprocally regulate their localization to endothelial cell-cell junctions. Association with RAP1 relocalizes KRIT1 from microtubules to cell junction membranes. TISSUE SPECIFICITY: Low levels in brain. Very weak expression found in heart and muscle. DOMAIN: The FERM domain mediates binding to RAP1A and RAP1B. DISEASE: Defects in KRIT1 are the cause of cerebral cavernous malformations type 1 (CCM1) [MIM:116860]. Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. CCMs have an incidence of 0.1%-0.5% in the general population and usually present clinically during the 3rd to 5th decade of life. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. SIMILARITY: Contains 4 ANK repeats. SIMILARITY: Contains 1 FERM domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRIT1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O00522
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001525 angiogenesis GO:0001937 negative regulation of endothelial cell proliferation GO:0007264 small GTPase mediated signal transduction GO:0010596 negative regulation of endothelial cell migration GO:0016525 negative regulation of angiogenesis GO:0032092 positive regulation of protein binding GO:0045454 cell redox homeostasis GO:0050790 regulation of catalytic activity GO:2000114 regulation of establishment of cell polarity GO:2000352 negative regulation of endothelial cell apoptotic process
US Server
